Abstract
The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. Administration of these promotes an increased transport of endogenous fatty acids to these organelles and a higher capacity of β-oxidation. Administration of 3-thia fatty acids to rats resulted in a significant decrease of the hepatic level of docosahexaenoic acid (DHA) (17–24%) and especially eicosapentaenoic acid (EPA) (40–80%) accompanied by increased gene expression of mitochondrial 2,4-dienoylCoA reductase and enoyl-CoA isomerase. The mitochondrial oxidation of EPA was increased more than 4-fold after administration of 3-thia fatty acids. EPA-CoA was a good substrate for mitochondrial carnitine acyltransferase-I and treatment with 3-thia fatty acids increased the activity 1.7-fold. DHA was a poor substrate for both mitochondrial and peroxisomal β-oxidation. DHA-CoA was a very poor substrate for mitochondrial carnitine acyltransferase-I and -II, and the activity did not increase after treatment. However, the peroxisomal DHA-CoA oxidase increased 10-fold after 3-thia fatty acid treatment, whereas the peroxisomal EPA-CoA oxidase increased only 5-fold. In isolated hepatocytes, 16% of total metabolized EPA was oxidized and 76% was incorporated into glycerolipids, whereas DHA was oxidized very little. We conclude that under conditions of increased mitochondrial and peroxisomal proliferation by 3-thia fatty acids, a relatively higher oxidation rate of polyunsaturated n–3 fatty acids might result in a decreased hepatic level of EPA and DHA. Under these conditions DHA seems to be oxidized by the peroxisomes, whereas EPA, which can be oxidized in both organelles, is mainly oxidized by mitochondria.—Madsen, L., L. Frøyland, E. Dyrøy, K. Helland, and R. K. Berge. Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation. J. Lipid Res.39: 583–593.
Highlights
The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators
Administration of C14-S-acetic acid to rats causes a decrease in the hepatic level of n–3 fatty acids and we have suggested that oleic acid and the ⌬9-desaturated metabolite of C14-S-acetic acid might displace the n–3 fatty acids from the sn -2 position in glycerolipids which renders them available for further metabolism by mitochondrial fatty acid oxidation [8]
The monocarboxylic C14-S-acetic acid, which is blocked for -oxidation acid, was incorporated in the liver in a dose-dependent manner, whereas the more effective peroxisome proliferator 3,10-dithiadicarboxylic acid (TD) which is blocked for both - and -oxidation, could not be detected
Summary
The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. EPA-CoA was a good substrate for mitochondrial carnitine acyltransferase-I and treatment with 3-thia fatty acids increased the activity 1.7-fold. We conclude that under conditions of increased mitochondrial and peroxisomal proliferation by 3-thia fatty acids, a relatively higher oxidation rate of polyunsaturated n–3 fatty acids might result in a decreased hepatic level of EPA and DHA. Under these conditions DHA seems to be oxidized by the peroxisomes, whereas EPA, which can be oxidized in both organelles, is mainly oxidized by mitochondria.—Madsen, L., L. N–3 fatty acids are incorporated into cell membranes in a highly selective way where they act as structural components influencing
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